Tay Sachs is a hereditary genetic disease caused by a mutation in the gene for the production of of the hexosaminidase A (Hex-A) protein.
The Hex-A Protein
The Hex-A protein is made up of two parts: alpha and beta. It also contains an activator subunit, which aids the protein in its function.
The function of the Hex-A protein is to break down fatty acids in the brain called the GM2 ganglioside, which accumulates primarily in the nerve cells. In short, the Hex-A protein is responsible for the prevention of fatty acid build ups in the brain.
Tay Sachs disrupts the function of the Hex-A protein, thus causing excessive deposits of fatty acids in the brain, causing brain damage.
Probability of the Disease
In humans, there are 23 pairs of chromosomes, each containing genetic information. The gene for the production of Hex-A is contained in chromosome 15.
It is possible to be a carrier of the Tay Sachs disease, without ever being affected by it. For carriers of the Tay Sach disease, only one of their chromosome 15 is mutated. Therefore, its non-mutated homologous chromosome can still be transcribed, and fully functional Hex-A proteins can still be produced.
The problem occurs, however, when both the homologous chromosomes are mutated. The person would be unable to produce a fully functional Hex-A protein, and therefore would be unable to break down fatty acids within the brain. The fatty acids accumulate over time, applies pressure to the brain, and eventually destroys brain cells.
For a child to be affected by the Tay Sachs disease, both of his parents must be carriers, and he must receive the mutated gene from both parents. The probabilities are illustrated below.
Picture taken from "Carrier Testing." National Tay-Sachs & Allied Diseases Association, Inc. 14 Feb. 2007
<http://www.ntsad.org/ >.
If one OR both parents are carriers, there is a 50% chance that the child will be a carrier. If both parents are carriers, there is a 25% chance that the child will be affected by Tay Sachs.
If only one parent is a carrier, then the child has 0% chance of being affected by Tay Sachs, since both chromosome 15's need to be mutated for Tay Sachs to have an affect.
The Mutation
The Tay Sachs mutation can be as small as a single-base mutation. A change in the base sequence of the gene can cause the wrong amino acid to be added to the polypeptide chain.
In Tay Sachs, the alpha part of Hex-A is affected. The wrong amino acid caused by a single base mutation would affect the way the protein folds, and therefore reducing its overall effectiveness. There are over 90 known possible mutations that will cause the Tay Sachs disease.
The affected Hex-A protein functions at approximately 50% of its normal speed. This causes an abnormal build up of fatty acids, leading to the degeneration of the brain.
Sources:
"NINDS Tay-Sachs Disease Information Page." "Tay-Sachs: What is It?"
Causes of Tay-Sach Diseases
Tay Sachs is a hereditary genetic disease caused by a mutation in the gene for the production of of the hexosaminidase A (Hex-A) protein.
The Hex-A Protein
The Hex-A protein is made up of two parts: alpha and beta. It also contains an activator subunit, which aids the protein in its function.
The function of the Hex-A protein is to break down fatty acids in the brain called the GM2 ganglioside, which accumulates primarily in the nerve cells. In short, the Hex-A protein is responsible for the prevention of fatty acid build ups in the brain.
Tay Sachs disrupts the function of the Hex-A protein, thus causing excessive deposits of fatty acids in the brain, causing brain damage.
Probability of the Disease
In humans, there are 23 pairs of chromosomes, each containing genetic information. The gene for the production of Hex-A is contained in chromosome 15.
Picture taken from "Bioethics glossary [Bioethics Council]." The Bioetheics Council. 14 February 2007
< http://www.bioethics.org.nz/about-bioethics/glossary/index.html>
It is possible to be a carrier of the Tay Sachs disease, without ever being affected by it. For carriers of the Tay Sach disease, only one of their chromosome 15 is mutated. Therefore, its non-mutated homologous chromosome can still be transcribed, and fully functional Hex-A proteins can still be produced.
The problem occurs, however, when both the homologous chromosomes are mutated. The person would be unable to produce a fully functional Hex-A protein, and therefore would be unable to break down fatty acids within the brain. The fatty acids accumulate over time, applies pressure to the brain, and eventually destroys brain cells.
For a child to be affected by the Tay Sachs disease, both of his parents must be carriers, and he must receive the mutated gene from both parents. The probabilities are illustrated below.
Picture taken from "Carrier Testing." National Tay-Sachs & Allied Diseases Association, Inc. 14 Feb. 2007
<http://www.ntsad.org/ >.
If one OR both parents are carriers, there is a 50% chance that the child will be a carrier.
If both parents are carriers, there is a 25% chance that the child will be affected by Tay Sachs.
If only one parent is a carrier, then the child has 0% chance of being affected by Tay Sachs, since both chromosome 15's need to be mutated for Tay Sachs to have an affect.
The Mutation
The Tay Sachs mutation can be as small as a single-base mutation. A change in the base sequence of the gene can cause the wrong amino acid to be added to the polypeptide chain.
In Tay Sachs, the alpha part of Hex-A is affected. The wrong amino acid caused by a single base mutation would affect the way the protein folds, and therefore reducing its overall effectiveness. There are over 90 known possible mutations that will cause the Tay Sachs disease.
The affected Hex-A protein functions at approximately 50% of its normal speed. This causes an abnormal build up of fatty acids, leading to the degeneration of the brain.
Sources:
"NINDS Tay-Sachs Disease Information Page."
"Tay-Sachs: What is It?"
Symptoms-->